Genome-wide association study of multiyear dynamic growth traits in hybrid Liriodendron identifies robust genetic loci associated with growth trajectories.

The genetic factors underlying growth traits differ over time points or stages. However, most current studies of phenotypes at single time points do not capture all loci or explain the genetic differences underlying growth trajectories. Hybrid Liriodendron exhibits obvious heterosis and is widely cultivated, although its complex genetic mechanism underlying growth traits remains unknown. A genome-wide association study (GWAS) is an effective method for elucidating the genetic architecture by identifying genetic loci underlying complex quantitative traits. In the present study, using a GWAS, we identified robust loci associated with growth trajectories in hybrid Liriodendron populations. We selected 233 hybrid progenies derived from 25 crosses for resequencing, and measured their tree height (H) and diameter at breast height (DBH) for 11 consecutive years; 192 972 high-quality single nucleotide polymorphisms (SNPs) were obtained. The dynamics of the multiyear single-trait GWAS showed that year-specific SNPs predominated, and only five robust SNPs for DBH were identified in at least three different years. Multitrait GWAS analysis with model parameters as latent variables also revealed 62 SNPs for H and 52 for DBH associated with the growth trajectory, displaying different biomass accumulation patterns, among which four SNPs exerted pleiotropic effects. All identified SNPs also exhibited temporal variations in effect sizes and inheritance patterns potentially related to different growth and developmental stages. The haplotypes resulting from these significant SNPs might pyramid favorable loci, benefitting the selection of superior genotypes. The present study provides insights into the genetic architecture of dynamic growth traits and lays a basis for future molecular-assisted breeding.

Assessment of fetal growth trajectory identifies infants at high risk of perinatal mortality.

OBJECTIVE: To analyze perinatal risks associated with three distinct scenarios of fetal growth trajectory in the latter half of pregnancy compared with a reference group. METHODS: This cohort study included women with a singleton pregnancy that delivered between 32 + 0 and 41 + 6 weeks' gestation and had two or more ultrasound scans, at least 4 weeks apart, from 18 + 0 weeks. We evaluated three different scenarios of fetal growth against a reference group, which comprised appropriate-for-gestational-age fetuses with appropriate forward-growth trajectory. The comparator growth trajectories were categorized as: Group 1, small-for-gestational-age (SGA) fetuses (estimated fetal weight (EFW) or abdominal circumference (AC) persistently < 10th centile) with appropriate forward growth; Group 2, fetuses with decreased growth trajectory (decrease of ≥ 50 centiles) and EFW or AC ≥ 10th centile (i.e. non-SGA) at their final ultrasound scan; and Group 3, fetuses with decreased growth trajectory and EFW or AC < 10th centile (i.e. SGA) at their final scan. The primary outcome was overall perinatal mortality (stillbirth or neonatal death). Secondary outcomes included stillbirth, delivery of a SGA infant, preterm birth, emergency Cesarean section for non-reassuring fetal status and composite severe neonatal morbidity. Associations were analyzed using logistic regression. RESULTS: The final study cohort comprised 5319 pregnancies. Compared to the reference group, the adjusted odds of perinatal mortality were increased significantly in Group 2 (adjusted odds ratio (aOR), 4.00 (95% CI, 1.36-11.22)) and Group 3 (aOR, 7.71 (95% CI, 2.39-24.91)). Only Group 3 had increased odds of stillbirth (aOR, 5.69 (95% CI, 1.55-20.93)). In contrast, infants in Group 1 did not have significantly increased odds of demise. The odds of a SGA infant at birth were increased in all three groups compared with the reference group, but was highest in Group 1 (aOR, 111.86 (95% CI, 62.58-199.95)) and Group 3 (aOR, 40.63 (95% CI, 29.01-56.92)). In both groups, more than 80% of infants were born SGA and nearly half had a birth weight < 3rd centile. Likewise, the odds of preterm birth were increased in all three groups compared with the reference group, being highest in Group 3, with an aOR of 4.27 (95% CI, 3.23-5.64). Lastly, the odds of composite severe neonatal morbidity were increased in Groups 1 and 3, whereas the odds of emergency Cesarean section for non-reassuring fetal status were increased only in Group 3. CONCLUSION: Assessing the fetal growth trajectory in the latter half of pregnancy can help identify infants at increased risk of perinatal mortality and birth weight < 3rd centile for gestation. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

[Effect of gestational weight gain on growth trajectory in children aged 0 to 3 years].

OBJECTIVE: To describe the growth trajectory of body mass index for age Z score(BAZ) in children aged 0 to 3 years and to explore the association between gestational weight gain and BAZ growth trajectory. METHODS: Based on a prospective cohort study, we recruited pregnant women in their early pregnancy into this study from 2013 to 2017 in Taicang of Jiangsu Province, tracked their weight changes until they gave birth, and calculated and evaluated their gestational weight gain(GWG) as appropriate, inadequate or excessive GWG based on Chinese GWG standard. Children's height/length and weight were measured at birth, 1, 3, 6, 8, 12, 18, 24, 30 and 36 months of age, and their BAZ scores were calculated. Group-based trajectory modeling(GBTM) was used for fitting BAZ trajectories. Multilevel Logistic regression was used to analyze the association between the level of GWG and BAZ growth trajectories. RESULTS: There were 1864 mother-child pairs in the study, and three groups of BAZ trajectories were fitted including slow growth trajectory(34.07%), appropriate growth trajectory(48.23%), and fast growth trajectory(17.70%). In univariate analysis, compared with children whose mothers had appropriate GWG, the children whose mothers had inadequate GWG were more likely in the group of slow growth trajectory(OR = 1.95, 95%CI 1.28-2.96), and the children whose mothers had excessive GWG were more likely in the group of fast growth trajectory(OR = 1.57, 95% CI 1.19-2.07). After adjusting for maternal pre-pregnancy body mass index(BMI) and parity, and the child's gender and birth weight, the children whose mothers gained in adequate GWG were more likely in the group of slow growth trajectory(OR = 1.84, 95%CI 1.19-2.84), while the association between excessive GWG and fast growth trajectory was not statistically significant(OR = 1.26, 95%CI 0.94-1.68). CONCLUSION: The BAZ trajectories of children aged 0-3 years can be categorized into slow, appropriate, and fast growth groups, and children's slow growth was associated with maternal inadequate GWG.

Growth Velocities Across Distinct Early Life Windows and Child Cognition: Insights from a Contemporary US Cohort.

OBJECTIVE: To evaluate the relative importance of overall and period-specific postnatal growth and their interaction with fetal growth on cognition in a generally well-nourished population. STUDY DESIGN: We included 1052 children from Project Viva, a prospective cohort in Boston, Massachusetts. Using linear spline mixed-effects models, we modeled length/height and body mass index (BMI) trajectories from birth to 7 years and estimated standardized overall (0-7 years) and period-specific growth velocities ie, early infancy (0-4 months), late infancy (4-15 months), toddlerhood (15-37 months), and early childhood (37-84 months). We investigated associations of growth velocities as well as their interactions with birthweight-for-gestational age on mid-childhood (mean age: 7.9 years) IQ, visual memory and learning, and visual motor ability. RESULTS: Greater overall height velocity was associated with modestly higher design memory score, (adjusted ß [95% CI] 0.19 [-0.01,0.38] P = .057])points per SD increase but lower verbal IQ (-0.88 [-1.76,0.00] P = .051). Greater early infancy height velocity was associated with higher visual motor score (1.92 [0.67,3.18]). Greater overall BMI velocity was associated with lower verbal IQ (-0.71 [-1.52,0.11] P = .090). Greater late infancy BMI velocity was associated with lower verbal IQ (-1.21 [-2.07,-0.34]), design memory score (-0.22 [-0.42,-0.03)], but higher picture memory score (0.22 [0.01,0.43]). Greater early infancy height velocity (-1.5 SD vs 1.5 SD) was associated with higher nonverbal IQ (margins [95% CI] 102.6 [98.9106.3] vs 108.2 [104.9111.6]) among small-for-gestational age infants (P-interaction = 0.04). CONCLUSIONS: Among generally well-nourished children, there might not be clear cognitive gains with faster linear growth except for those with lower birthweight-for-gestational age, revealing the potential importance of early infancy compensatory growth.

Timing of gestational diabetes diagnosis, gestational weight gains and offspring growth trajectory: a prospective birth cohort study.

BACKGROUND: The evidence on the associations of the timing of maternal gestational diabetes mellitus (GDM) with the comprehensive growth trajectory from perinatal to early childhood in offspring is limited. The potential mechanism remains elusive. Our aim is to estimate the associations of the timing of GDM diagnosis and gestational weight gains (GWG) with the growth trajectory of children from perinatal to early childhood. METHODS: A total of 7609 participants are included from the Maternal & Infants Health in Hefei cohort study. Primary predictors were the timing of maternal GDM diagnosis and GWG during pregnancy. The main outcomes included fetal ultrasonic measurements, birth size as well as BMI peak indicators during infancy within 48 months. RESULTS: GDM diagnosed before 26 weeks was associated with increased risks of overgrowth for fetal abdominal circumference (OR 1.19, 95% CI 1.04-1.36) and birth weight (OR 1.51, 95% CI 1.19-1.91) when compared with unexposed. GDM diagnosis < 26 weeks was related to the higher BMI peak (ß 0.16, 95%CI 0.03-0.28) within 48 months. The significantly additive impacts of maternal early GDM diagnosis and excessive gestational weight gains (EGWG) on offspring overgrowth were observed. Women in GDM < 26 weeks with early EGWG group had higher levels of hsCRP compared with GDM > 26 weeks (P < 0.001). CONCLUSIONS: Exposure to maternal GDM diagnosed before 26 weeks with early EGWG could lead to shifts and/or disruptions from the typical growth trajectory from perinatal to early childhood in offspring.

Breastfeeding duration and associations with prevention of accelerated growth among infants from low-income, racially and ethnically diverse backgrounds.

OBJECTIVE: To describe breastfeeding rates from early to late infancy and to examine associations between breastfeeding duration and infant growth, including rapid weight gain (RWG, > 0·67 SD increase in weight-for-age Z-score), among infants from low-income, racially and ethnically diverse backgrounds. DESIGN: A short, prospective cohort study was conducted assessing breastfeeding status at infant ages 2, 4, 6, 9 and 12 months. Infant length and weight measurements were retrieved from electronic health records to calculate weight-for-length Z-scores and the rate of weight gain. SETTING: Pediatric clinic in the Southeastern USA. PARTICIPANTS: Mother-infant dyads (n = 256). RESULTS: Most participants were African American (48 %) or Latina (34 %). Eighty-one per cent were participating in the Special Supplemental Nutrition Program for Women, Infants and Children. Infants were breastfed for a median duration of 4·75 months, with partial more common than exclusive breastfeeding. At 12 months, 28 % of the participants were breastfeeding. Infants breastfed beyond 6 months had significantly lower growth trajectories than infants breastfed for 0-2 months (ß = 0·045, se = 0·013, P = 0·001) or 3-6 months (ß = 0·054, se = 0·016, P = 0·001). Thirty-six per cent of the infants experienced RWG. RWG was more common among infants who were breastfed for 2 months or less than 6+ month breastfed group (relative risk = 1·68, CI95 (1·03, 2·74), P = 0·03). CONCLUSIONS: Breastfeeding beyond 6 months is associated with the prevention of accelerated growth among infants from low-income, racially and ethnically diverse backgrounds, suggesting progress toward health equity.

Late preterm birth and growth trajectories during childhood: a linked retrospective cohort study.

BACKGROUND: Evidence suggests that accelerated postnatal growth in children is detrimental for adult cardiovascular health. It is unclear whether children born late preterm (34-36 weeks) compared to full term (≥ 39 weeks), have different growth trajectories. Our objective was to evaluate the association between gestational age groups and growth trajectories of children born between 2006-2014 and followed to 2021 in Ontario, Canada. METHODS: We conducted a retrospective cohort study of children from singleton births in TARGet Kids! primary care network with repeated measures of weight and height/length from birth to 14 years, who were linked to health administrative databases. Piecewise linear mixed models were used to model weight (kg/month) and height (cm/month) trajectories with knots at 3, 12, and 84 months. Analyses were conducted based on chronological age. RESULTS: There were 4423 children included with a mean of 11 weight and height measures per child. The mean age at the last visit was 5.9 years (Standard Deviation: 3.1). Generally, the more preterm, the lower the mean value of weight and height until early adolescence. Differences in mean weight and height for very/moderate preterm and late preterm compared to full term were evident until 12 months of age. Weight trajectories were similar between children born late preterm and full term with small differences from 84-168 months (mean difference (MD) -0.04 kg/month, 95% CI -0.06, -0.03). Children born late preterm had faster height gain from 0-3 months (MD 0.70 cm/month, 95% CI 0.42, 0.97) and 3-12 months (MD 0.17 cm/month, 95% CI 0.11, 0.22). CONCLUSIONS: Compared to full term, children born late preterm had lower average weight and height from birth to 14 years, had a slightly slower rate of weight gain after 84 months and a faster rate of height gain from 0-12 months. Follow-up is needed to determine if growth differences are associated with long-term disease risk.

Rhesus macaque fetal and placental growth demographics: A resource for laboratory animal researchers.

Rhesus macaques (Macaca mulatta) are amongst the most common nonhuman primate species used in biomedical research. These animals provide a precious resource for translational studies and opportunities to maximize rhesus data use are encouraged. Here we compile data produced from 10 years of investigator-driven pregnancy studies conducted at the Oregon National Primate Research Center (ONPRC). All pregnancies were generated within the consistent and reproducible protocols of the ONPRC time-mated breeding program. The data included are from control animals who did not experience in utero perturbations or experimental manipulations. A total of 86 pregnant rhesus macaques were delivered by cesarean section over a range of gestational days (G) 50 to G159 (where term is G165 ± 10 days in the rhesus macaque), with subsequent immediate tissue harvesting following standardized protocols. Fetal and placental growth measures, and all major organ weights are reported. All data are presented relative to gestational age for the entire cohort and in addition, data are stratified by fetal sex. The outcome is a large reference resource for use by laboratory animal researchers in future comparative fetal development studies.

Early growth trajectory is associated with psychological stress in parents of infants with congenital heart disease, but moderated by quality of partner relationship.

PURPOSE: To explore the relationships between growth trajectory, parenting stress and parent post-traumatic stress (PTS), in infants with congenital heart disease, and the moderating role of parents' dyadic adjustment on those associations. DESIGN AND METHODS: A secondary analysis of data from the REACH Telehalth home monitoring multi-site randomized clinical trial. Parents completed the Parenting Stress Index (PSI), Post-traumatic diagnostic scale, and the Dyadic Adjustment Scale. Multivariate logistic regression models were used to examine the associations of interest. RESULTS: During 4-month follow-up after hospital discharge, parents of infants with 'Never recovered' and 'Partially recovered' growth trajectories had 2-5 times higher odds of experiencing higher stress on the Parent Domain (OR = 4.8, CI = 1.3-18.0; OR = 2.5, CI = 1.0-5.9, respectively) than those with stably grown infants. Parents of "Never recovered" infants had 4 times higher odds of PTS symptoms (OR = 3.9; CI = 1.6-9.9). Parental dyadic adjustment moderated the relationships. Parents of 'Partially recovered' infants and having low dyadic adjustment had 3-5 times higher odds of high stress on all PSI domains, while parents with high dyadic adjustment did not have increased stress due to poor infant growth. Parents of "Never recovered" infants had four times higher odds of PTS symptom, even with high dyadic adjustment. CONCLUSIONS: Infant growth trajectory over the first four months is associated with parenting stress and PTS. Quality of partner relationship moderates some of these associations. PRACTICE IMPLICATIONS: Infant growth should serve as a screening aid for identifying parents at psychological risk. Interventions targeting the quality of partner relationship may support parental coping and mitigate stress. CLINICAL TRIAL REGISTRATION: NCT01941667.

Analysis of Growth Trajectories and Verification of Related SNPs in Populus deltoides.

As an important timber genus with high economic and ecological values, Populus is a model for dissecting the genetic architecture of growth traits in perennial forest trees. However, the genetic mechanisms of longitudinal growth traits in poplar remain incompletely understood. In this study, we conducted longitudinal genetic analysis of height and diameter at breast height (DBH) in eleven-year poplar clones using ultra-deep sequencing datasets. We compared four S-shaped growth models, including asymptotic, Gompertz, logistic, and Richard, on eleven-year height and DBH records in terms of five metrics. We constructed the best-fitting growth model (Richard) and determined poplar ontogenetic stages by virtue of growth curve fitting and likelihood ratio testing. This study provides some scientific clues for temporal variation of longitudinal growth traits in Populus species.

Effects of maternal urban particulate matter SRM 1648a exposure on birth outcomes and offspring growth in mice.

The association between exposure to particulate matter (PM) during pregnancy and abnormal birth outcomes is still inconclusive. This study aims to provide more evidence for this public health concern by investigating birth outcomes and the growth of offspring in mice exposed to PM during pregnancy. C57BL/6 J pregnant mice were exposed to PM via nasal drip at three doses or solvent control. The dam weight gain was recorded during pregnancy. The number of pups, pup weight, and placental weight were recorded at embryonic day 18.5 (E18.5) necropsy. For mice that gave birth naturally, we calculated the gestation length and measured the body weight of offspring once a week from the 1st to the 6th week after birth. The results showed that there were no significant differences in maternal body weight gain, conception rate, pregnancy duration, and litter size among different groups. There were no significant differences in fetal weight, placental weight, and fetal/placental weight ratio at E18.5. Weight gain in offspring was reduced after birth. The average body weight of offspring in the high-dose group was significantly lower than that in the control group at weeks 5 in female pups. There were no significant differences in the body weight of male offspring among groups from 1st to the 6th. Together, our study indicated that maternal exposure to PM did not significantly impact birth outcomes of C57BL/6 J mice but affected growth trajectories in offspring after birth in a dose- and fetal sex-dependent manner.

Anthropometry, body composition, early growth and chronic disease risk factors among Zambian adolescents exposed or not to perinatal maternal HIV.

Early life exposures and growth patterns may affect long-term risk of chronic non-communicable diseases (NCD). We followed up in adolescence two Zambian cohorts (n 322) recruited in infancy to investigate how two early exposures - maternal HIV exposure without HIV infection (HEU) and early growth profile - were associated with later anthropometry, body composition, blood lipids, Hb and HbA1c, blood pressure and grip strength. Although in analyses controlled for age and sex, HEU children were thinner, but not shorter, than HIV-unexposed, uninfected (HUU) children, with further control for socio-demographic factors, these differences were not significant. HEU children had higher HDL-cholesterol than HUU children and marginally lower HbA1c but no other biochemical or clinical differences. We identified three early growth profiles - adequate growth, declining and malnourished - which tracked into adolescence when differences in anthropometry and body fat were still seen. In adolescence, the early malnourished group, compared with the adequate group, had lower blood TAG and higher HDL, lower grip strength (difference: -1·87 kg, 95 % CI -3·47, -0·27; P = 0·02) and higher HbA1c (difference: 0·5 %, 95 % CI 0·2, 0·9; P = 0·005). Lower grip strength and higher HbA1c suggest the early malnourished children could be at increased risk of NCD in later life. Including early growth profile in analyses of HIV exposure reduced the associations between HIV and outcomes. The results suggest that perinatal HIV exposure may have no long-term effects unless accompanied by poor early growth. Reducing the risk of young child malnutrition may lessen children's risk of later NCD.

Prenatal phthalate exposure associated with age-specific alterations in markers of adiposity in offspring: A systematic review.

Childhood obesity and metabolic disorders are of concern and are public health problems globally. Environmental endocrine disruptors, including phthalates, are well known as "obesogens" and "metabolic disruptors". Several studies have investigated the relationships between prenatal phthalate exposure and childhood obesity with inconsistent conclusions. Given the child growth trajectory/pattern as a possible early marker of metabolic disorders, we aimed to assess the effect of prenatal phthalate exposure on offspring growth trajectory. A systematic literature search was conducted using MEDLINE (accessed through PubMed), Web of Science, and CNKI (Chinese National Knowledge Infrastructure) until July 2021. We evaluated the risk of bias for adherence to the prespecified criteria. Fourteen eligible articles were finally included in this systematic review according to the defined PECOS statement. The risk of bias of the included studies was "low" or "probably low", and few were "probably high" and "high". These studies were mostly carried out in the United States (N = 6); others were conducted in China (N = 2), Mexico (N = 2), France (N = 1), Spain (N = 1), Greece (N = 1), and Australia (N = 1) and published from 2015 to 2021. The combined subjects of the 14 studies were 10,396 mother-child pairs. Except for 3 studies not reporting the sex ratio, at least 4001 boys and 3366 girls were included. For the association of prenatal phthalate exposure with an absolute adiposity marker (at a specific visit timepoint), only a few studies were using the same obesity marker as the outcome endpoint and using the same statistical method to explore their associations. However, MEP appeared to be positively associated with several obesity markers, such as the absolute BMI z score, weight-for-age z score, waist circumference, and overweight status. For the association of prenatal phthalate exposure with a repeated measurement of the adiposity marker over the age range, neither associations of adiposity markers with a specific phthalate metabolite nor relationships of a specific adiposity marker with prenatal phthalate exposure were of a consistent result. All four articles reported that phthalate metabolite exposure during pregnancy was associated with children's growth trajectory. Three suggested a sex-specific association between prenatal phthalate exposure and obesity trajectory. In conclusion, the current articles did not show any relationship between prenatal phthalate exposure and children's age-specific outcomes, except for positive associations of prenatal MEP exposure with absolute adiposity markers. However, epidemiological data supported a weak relationship between prenatal phthalate exposure and children's obesity trajectory in a sex-specific manner.

Prenatal single and combined exposure to phthalates associated with girls' BMI trajectory in the first six years.

Evidence of the influence of prenatal phthalate exposure on childhood longitudinal obesity markers is limited. Nested on the Ma'anshan birth cohort study, 990 mother-daughter pairs were included. Seven phthalate metabolites were determined in urine collected in each trimester. Each child underwent a physical examination from birth to 6 years of age twelve times. Latent class growth models were used to identify three trajectories of girls' body mass index (BMI). Logistic regression, quantile g-computation and Bayesian kernel machine regression models analyzed the relationships of prenatal exposure to individual and mixed phthalates with girls' body mass index (BMI) trajectory. Compared to the "lowest trajectory" class, prenatal average concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP, ORcrude = 2.095, 95 % CI = 1.014-4.328) and di(2-ethylhexyl) phthalate (DEHP, ORcrude = 2.336, 95 % CI = 1.022-5.338) during pregnancy were associated with an increased probability of being in the "highest trajectory" class. The average concentration of DEHP (ORcrude = 1.879, 95 % CI = 1.002-3.522) was associated with an increased probability of being in the "moderate trajectory" class. Stratified analyses by trimester of pregnancy mainly showed that third-trimester exposure to monoethyl phthalate (MEP, ORadjusted = 1.584, 95 % CI = 1.094-2.292), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP, ORadjusted = 2.885, 95 % CI = 1.367-6.088), MEHHP (ORadjusted = 2.425, 95 % CI = 1.335-4.407), DEHP (ORadjusted = 2.632, 95 % CI = 1.334-5.193) and high molecular weight phthalate (ORadjusted = 2.437, 95 % CI = 1.239-4.792) was associated with an increased probability of being in the "highest trajectory" class. However, the mixture of phthalates was not significantly related to the girl's BMI trajectory. In conclusion, in utero exposure to phthalates, including MEP and DEHP metabolites (MEHHP and MEOHP), was significantly associated with early childhood high BMI trajectories in girls. The third trimester of pregnancy seemed to be the window of vulnerability to phthalate exposure for girls' high BMI trajectory at periods of prenatal development. No evidence supported a significant relationship between combined exposure to phthalate metabolites and girls' high BMI trajectory.

New insights on growth trajectory in infants with complex congenital heart disease.

PURPOSE: We aimed to describe the weight-for-age Z-score growth trajectory (WAZ-GT) of infants with complex congenital heart disease (cCHD) after neonatal cardiac surgery in the first 4 months of life and assess potential risk factors. METHODS: We utilized data from a previously reported trial of the REACH telehealth home monitoring (NCT01941667) program which evaluated 178 infants with cCHD from 2012 to 2017. Over the first 4 months of life, weekly infant weights were converted to WAZ. WAZ-GT classes were identified using latent class growth modeling. Multinomial logistic regression models were used to examine the associations between potential risk factors and WAZ-GT classes. RESULTS: Four distinct classes of WAZ-GT were identified: maintaining WAZ > 0, 14%; stable around WAZ = 0, 35%; partially recovered, 28%; never recovered, 23%. Compared with reference group "stable around WAZ=0," we identified clinical and sociodemographic determinants of class membership for the three remaining groups. "Maintaining WAZ > 0" had greater odds of having biventricular physiology, borderline appetite, and a parent with at least a college education. "Partially recovered" had greater odds of hospital length of stay>14 days and being a single child in the household. "Never recovered" had greater odds hospital length of stay >14 and > 30 days, tube feeding at discharge, and low appetite. CONCLUSIONS: This study described distinct classes of WAZ-GT for infants with cCHD early in infancy and identified associated determinants. PRACTICE IMPLICATIONS: Findings from this study can be used in the identification of infants at risk of poor WAZ-GT and in the design of interventions to target growth in this vulnerable patient population.

Sex-dependent associations of maternal androgen levels with offspring BMI and weight trajectory from birth to early childhood.

CONTEXT: In preclinical studies, high androgen levels during pregnancy are associated with low birth weight and rapid postnatal weight gain in the offspring. However, human data linking prenatal androgens with birth weight and early life weight gain in the offspring are scarce. DESIGN: We evaluated 516 mother-child pairs enrolled in the New England birth cohorts of the Collaborative Perinatal Project (1959-1966). We assayed androgen bioactivity in maternal sera during third-trimester using a receptor-mediated luciferase expression bioassay. Age and sex-specific BMI Z-scores (BMIz), defined using established standards, were assessed at birth, 4 months, 1 year, 4 years, and 7 years. We used linear mixed models to evaluate the relation of maternal androgens with childhood BMIz overall and by sex. We examined the association of maternal androgens with fetal growth restriction. The association of weight trajectories with maternal androgens was examined using multinomial logistic regression. RESULTS: Higher maternal androgen levels associated with lower BMIz at birth (ß = - 0.39, 95% CI: - 0.73, - 0.06); this relation was sex-dependent, such that maternal androgens significantly associated with BMIz at birth in girls alone (ß = - 0.72, 95% CI: - 1.40, - 0.04). The relation of maternal androgens with fetal growth restriction revealed dose threshold effects that differed by sex. There was no significant association between maternal androgens and weight trajectory overall. However, we found a significant sex interaction (p = 0.01); higher maternal androgen levels associated with accelerated catch-up growth in boys (aOR = 2.14, 95% CI: 1.14, 4.03). CONCLUSION: Our findings provide evidence that maternal androgens may have differential effects on the programming of intrauterine growth and postnatal weight gain depending on fetal sex.

Body mass index trajectories up to preschool age in a multi-ethnic population; relations with maternal gestational diabetes, BMI and gestational weight gain.

AIM: Independent effects of gestational diabetes (GDM), maternal prepregnant obesity and gestational weight gain on offspring BMI and obesity are scarcely documented. We examined associations between GDM and children's BMI trajectories from birth to 4-5 years age, and effects of prepregnant obesity and gestational weight gain not mediated through GDM. METHODS: We included 734 children from a population-based, multi-ethnic cohort of women and their offspring followed from early pregnancy. All women were screened for GDM. Using linear mixed models, we explored associations between maternal factors and children's BMI development through seven serial measurements. RESULTS: At birth and age 4-5 years, BMI of children exposed to GDM was similar to those not exposed. However, they had slower BMI growth (B = -0.1 BMI units/month (95% CI: -0.17, -0.04)) during first 6 months, and faster BMI growth from 6 months to 4-5 years. Maternal prepregnant obesity was associated with higher child BMI at birth, and thereafter persistently higher BMI. High gestational weight gain was associated with faster BMI growth from 6 months to 4-5 years. CONCLUSION: Effects of maternal GDM, prepregnant obesity, and gestational weight gain on children's BMI and BMI trajectories from birth to preschool age differed in relation to effect size, timing and direction.

Growth Velocity and Doppler Evaluation to Predict Nonreassuring Fetal Heart Rate at Birth in Low-Risk Women: A Prospective, Longitudinal Study.

INTRODUCTION: This study investigated whether fetal growth deceleration in term, appropriate-for-gestational-age (AGA) fetuses is associated with placental insufficiency and nonreassuring fetal heart rate (NRFHR) at birth. METHODS: In this prospective study, 246 low-risk, singleton pregnancies at term with AGA fetuses were recruited. Correlation between decreased growth velocity (decline in estimated fetal weight [EFW] percentile), low EFW (EFWQ1 = latest EFW between 11 and 25% percentiles), umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, and cerebro-placental ratio (CPR) with cesarean and instrumental deliveries due to NRFHR were tested. RESULTS: The median change between fetal weight estimates (percentiles/week) was +0.49% (95% CI: -4 to +5%). Ten percent had decreased EFW percentile >3.5%/week. Fetal growth velocity/week was associated with MCA (r = 0.21, p < 0.001) and CPR (r = 0.24, p < 0.001) and inversely correlated with UA PI (r = -0.28, p < 0.001). NRFHR and cesarean section (CS) rates due to NRFHR were associated with decreased growth velocity, EFWQ1, and low CPR. The combination of abnormal CPR with decreased growth velocity occurred in 12 pregnancies, of which 5 (42%) had urgent CS due to NRFHR. The combination of abnormal CPR with EFWQ1 occurred in 9 pregnancies, of which 4 (44%) had urgent CS due to NRFHR. These combinations increased the likelihood ratio of CS due to NRFHR two-fold (8.41; 2.54-24.5) but did not significantly alter the number needed to treat by elective CS (3.78-4.68). CONCLUSION: Fetal growth velocity, EFW between 10 and 25th percentiles (EFWQ1), and abnormal CPR improves prediction of unplanned CS due to NRFHR among term AGA fetuses. This should be considered when counseling about the delivery method.

Analysis of the external acoustic meatus for ergonomic design: part II - anthropometric variations of the external acoustic meatus by sex, age and side in Chinese population.

For devices worn inside the ear, detailed anthropometric data of the external acoustic meatus (EAM) is needed, yet lacking due to the complex and costly methodology associated with attaining such measurements. The purpose of this study was to provide the anthropometric characteristics of the EAM including variations by age group, sex, and side (right/left). 1400 external ears (700 Chinese subjects) were casted and scanned. A total of 23 EAM dimensions of length, width, angle, circumference and area were measured, most of which changed by age group, sex and side. 19 measurements were larger in males and 17 measurements were larger in left-side ears. Except the entrance length and circumference, measurements were not statistically significant between left- and right-side ears. This study provides key anthropometric measurements of the EAM in a Chinese population which can be used for ergonomic design purposes. Practitioner summary: This study provides an available source for anthropometric variations of the external acoustic meatus by age, gender and side in the Chinese population, which can be used as a reference to improve the fit, comfort and function of in-ear wearable devices.

The duration of embryo culture after mouse IVF differentially affects cardiovascular and metabolic health in male offspring.

STUDY QUESTION: Do the long-term health outcomes following IVF differ depending upon the duration of embryo culture before transfer? SUMMARY ANSWER: Using a mouse model, we demonstrate that in male but not female offspring, adverse cardiovascular (CV) health was more likely with prolonged culture to the blastocyst stage, but metabolic dysfunction was more likely if embryo transfer (ET) occurred at the early cleavage stage. WHAT IS KNOWN ALREADY: ART associate with increased risk of adverse CV and metabolic health in offspring, and these findings have been confirmed in animal models in the absence of parental infertility issues. It is unclear which specific ART treatments may cause these risks. There is increasing use of blastocyst, versus cleavage-stage, transfer in clinical ART which does not appear to impair perinatal health of children born, but the longer-term health implications are unknown. STUDY DESIGN, SIZE, DURATION: Five mouse groups were generated comprising: (i) natural mating (NM)-naturally mated, non-superovulated and undisturbed gestation; (ii) IV-ET-2Cell-in-vivo derived two-cell embryos collected from superovulated mothers, with immediate ET to recipients; (iii) IVF-ET-2Cell-IVF generated embryos, from oocytes from superovulated mothers, cultured to the two-cell stage before ET to recipients; (iv) IV-ET-BL-in-vivo derived blastocysts collected from superovulated mothers, with immediate ET to recipients; (v) IVF-ET-BL-IVF generated embryos, from oocytes from superovulated mothers, cultured to the blastocyst stage before ET to recipients. Both male and female offspring were analysed for growth, CV and metabolic markers of health. There were 8-13 litters generated for each group for analyses; postnatal data were analysed by multilevel random effects regression to take account of between-mother and within-mother variation and litter size. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: C57/BL6 female mice (3-4 weeks old) were used for oocyte production; CBA males for sperm with human tubal fluid medium were used for IVF. Embryos were transferred (ET) to MF1 pseudo-pregnant recipients at the two-cell stage or cultured in synthetic oviductal medium enriched with potassium medium to the blastocyst stage before ET. Control in-vivo embryos from C57BL6 × CBA matings were collected and immediately transferred at the two-cell or blastocyst stage. Postnatal assays included growth rate up to 27 weeks; systolic blood pressure (SBP) at 9, 15 and 21 weeks; lung and serum angiotensin-converting enzyme (ACE) activity at time of cull (27 weeks); glucose tolerance test (GTT; 27 weeks); basal glucose and insulin levels (27 weeks); and lipid accumulation in liver cryosections using Oil Red O imaging (27 weeks). MAIN RESULTS AND THE ROLE OF CHANCE: Blastocysts formed by IVF developed at a slower rate and comprised fewer cells that in-vivo generated blastocysts without culture (P < 0.05). Postnatal growth rate was increased in all four experimental treatments compared with NM group (P < 0.05). SBP, serum and lung ACE and heart/body weight were higher in IVF-ET-BL versus IVF-ET-2Cell males (P < 0.05) and higher than in other treatment groups, with SBP and lung ACE positively correlated (P < 0.05). Glucose handling (GTT AUC) was poorer and basal insulin levels were higher in IVF-ET-2Cell males than in IVF-ET-BL (P < 0.05) with the glucose:insulin ratio more negatively correlated with body weight in IVF-ET-2Cell males than in other groups. Liver/body weight and liver lipid droplet diameter and density in IVF-ET-2Cell males were higher than in IVF-ET-BL males (P < 0.05). IVF groups had poorer health characteristics than their in-vivo control groups, indicating that outcomes were not caused specifically by background techniques (superovulation, ET). No consistent health effects from duration of culture were identified in female offspring. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Results from experimental animal models cannot be extrapolated to humans. Nevertheless, they are valuable to develop conceptual models, in this case, in the absence of confounding parental infertility, in assessing the safety of ART manipulations. WIDER IMPLICATIONS OF THE FINDINGS: The study indicates that longer duration of embryo culture after IVF up to blastocyst before ET leads to increased dysfunction of CV health in males compared with IVF and shorter cleavage-stage ET. However, the metabolic health of male offspring was poorer after shorter versus longer culture duration. This distinction indicates that the origin of CV and metabolic health phenotypes after ART may be different. The poorer metabolic health of males after cleavage-stage ET coincides with embryonic genome activation occurring at the time of ET. STUDY FUNDING/COMPETING INTEREST(S): This work was supported through the European Union FP7-CP-FP Epihealth programme (278418) and FP7-PEOPLE-2012-ITN EpiHealthNet programme (317146) to T.P.F., the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/F007450/1) to T.P.F., and the Saudi government, University of Jeddah and King Abdulaziz University to A.A. The authors have no conflicts of interest to declare.